The major event in the development of the profound immune deficiency characteristic of AIDS is the depletion of CD4 T lymphocytes resulting from infection with the human immunodeficiency virus (HIV). However, it has become apparent that infection with HIV does not necessarily result in full-blown AIDS. Infected individuals may be asymptomatic carriers, indicating that the virus may remain quiescent for periods of time. The biologic basis for the diversity of HIV-related disease outcomes is not known. However, the rapid quantitative response of CD8 T cells to HIV infection and the possible effectiveness of these cells in limiting HIV replication suggest an immunologic mechanism for the control of HIV. The goal of the proposed research is to characterize the role of CD8 T cells in the control of HIV infection and to identify mechanisms or defects involving CD8 cells that accompany progression of HIV infection to AIDS. We hypothesize that defective CD8 mechanisms contribute to the development of AIDS and that infection with the herpesviruses cytomegalovirus (CMV) and herpes simplex virus (HSV) is a factor in the defective CD8 response. We will use functional assays for CD8-mediated suppression and develop appropriate assays for assessing cytotoxicity in order to define the function of separated CD8 subsets and cloned CD8 cells that may be important in the response to HIV. We will compare CD8 responses in children and adults. In contrast to adults with HIV infection, many children do not have the putative co-factor of herpesvirus infections and are immunologically naive when infected. We will also develop an in vitro system in which to define the responses of cord and adult CD8 cells to HIV and the role of CMV or HSV in altering that response. The identification of specific immunological aspects of HIV infection that contribute to control or progression of disease will add significant?y to the understanding of HIV-related illness and provide insight into effective ways to combat it.